Home
Login
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
Publ. Version/Full Text
Research data
DOI
PMC
 |
Open Access Hybrid |
|
as soon as is submitted to ZB.
The binding of 3-O-methylfluorescein phosphate to the catalytic domain of the human CDC25B phosphatase: A structural investigation.
ChemBioChem 27:e202600010 (2026)
The molecular mechanisms by which the human CDC25B activates the CDK1/cyclin B complex in the cell cycle, as well as how it can be inhibited by synthetic inhibitors at the atomic level, are still under investigation. Valuable insights have been gained from the molecular structure here-described, which captures for the first time the interaction between the C-terminal domain of the inactive mutant CDC25B C473S (CDC25B-S) and the commonly used synthetic substrate 3-O-methylfluorescein phosphate (3-OMFP). Crystallographic studies reveal that 3-OMFP engages multiple residues within the active site and the adjacent "swimming pool" of CDC25B-S, establishing specific interactions and prompting local adjustments in this region. These structural features explain the increased resistance to thermal denaturation of CDC25B-S observed through circular dichroism measurements upon substrate binding. The structural changes induced by 3-OMFP lead to a conformation comparable to that of CDC25A bound to its substrate, the CDK2/cyclin A complex. These findings qualify 3-OMFP as a promising starting model for the rational design of selective competitive inhibitors of CDC25B having reduced off-target effects.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
3‐omfp ; Cdc25b ; Crystal Structure ; Ligand Binding ; Structural Basis For Inhibitor Design; Dual-specificity Phosphatases; Cell-cycle Control; Crystal-structure; Phase-transition; In-vitro; Inhibition; Discovery; Dynamics; Docking; Kinases
ISSN (print) / ISBN
1439-4227
e-ISSN
1439-7633
Journal
ChemBioChem
Quellenangaben
Volume: 27,
Issue: 7,
Article Number: e202600010
Publisher
Wiley
Publishing Place
Postfach 101161, 69451 Weinheim, Germany
Reviewing status
Peer reviewed
Institute(s)
Institute of Structural Biology (STB)
Grants
European Synchrotron Radiation Facility (ESRF)